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Efficacy of reboxetine in patients with severe major depression
S226
PI Aflective disorders andantidepressants
Results: Statistically significant differences were not seen at end point; however, they were noted for response on the MADRS total and CGI-I scores, but not on the HAM-D. In addition, by week 4, venlafaxine was statistically significantly (P < 0.05) superior to fluoxetine and placebo in reducing the HAM-D depressed mood item. At week 4, a trend toward venlafaxine superiority in reducing the HAM-D psychic anxiety item was observed (P = 0.059). By week 6, MADRS response frequency was 55%, 36%, and 36% for venlafaxine, fluoxetine, and placebo, respectively (P < 0.05 venlafaxine vs placebo; P < 0.05 venlafaxine vs fluoxetine). By week 3, CGI-I response frequency was 50%, 41%, and 35% for venlafaxine, fluoxetine, and placebo, respectively (P < 0.05 venlafaxine vs placebo; P < 0.05 venlafaxine vs fluoxetine). A separate analysis of the MADRS data suggests that the superior efficacy of venlafaxine over fluoxetine or placebo increases in direct proportion to the baseline score (ie, the sicker the patient, the greater the venlafaxine efficacy). Venlafaxine produced a higher remission rate than fluoxetine and placebo (42%, 29%, and 38%, respectively), a trend level that did not reach statistical significance. Although the incidence of individual adverse events was modestly higher in the venlafaxine group, both venlafaxine and fluoxetine were well tolerated in these geriatric patients. Conclusion: Although significant differences in overall effects were not seen at week 8, venlafaxine showed increased response on CGI-I by week 3, depressed mood and psychic anxiety by week 4, and MADRS at week 6. These data suggest venlafaxine had a more rapid onset of action, demonstrating a significantly greater response than fluoxetine as early as week 3. No significant safety concerns were evident at the maximum administered doses of either study drug in these patients.
[P.1.022/ Effects of reboxetine on HAM-D factors among depressed patients J. Ferguson, J. Mendels, S. Montgomery, S. Stahl, G. Schwartz*. Pharmacia & Upjohn, Global Medical Aflairs, Peapack, New Jersey, USA Background: Reboxetine selectively blocks reuptake of noradrenaline and has been shown to be effective for the treatment of major depressive disorder. We have examined the effects of reboxetine on several HAM-D symptom clusters. Methods: The effects of reboxetine 8 to 10 mg/day on symptom clusters were examined from short-term, double-blind, randomized, placebo-controlled trials. Mean change from baseline at each assessment interval was determined for the anxiety factor (HAMD items 10, 11, 12, 13, 15, 17), insomnia factor (items 4, 5, 6), cognitive disturbance factor (items 2, 3 9, 19, 20, 21), and psychomotor retardation factor (items 1, 7, 8, 14). In addition, symptom clusters were examined for dichotomous changes associated with an increase or decrease in symptoms Tom baseline. Results: Significant improvements Tom baseline were observed for HAM-D anxiety factor I as early as day 14, and these improvements were maintained to the end of the trials. Significant improvements from baseline were also observed with reboxetine for other HAM-D symptom clusters, which will be reported in detail. Conclusion: Reboxetine was associated with substantial improvements from baseline in symptoms of anxiety, insomnia, cognition, and retardation. These results support the effectiveness of reboxetine for the treatment of major depression irrespective
of initial symptom profile and demonstrate additional beneficial improvements in specific symptom clusters.
)p.1.0231
Efficacy of reboxetine in patients with severe major depression
S. Montgomery, S. Stahl, J. Ferguson, J. Mendels, G. Schwartz*. Pharmacia & Upjohn, Global Medical Affairs, Peapack New Jersey, USA Background: Reboxetine is a novel antidepressant that selectively inhibits the reuptake of noradrenaline without significant effects on the serotonin transporter. Results from several placebocontrolled trials in patients with major depressive disorder have demonstrated efficacy for reboxetine. Although efficacy has been shown for the total group of depressed patients in clinical trials, we are presenting the analysis of a subset of patients with severe depression. Methods: An analysis was conducted of the efficacy of reboxetine in the subgroup of clinical trial participants with severe depression, defined as having a HAM-D Rating Scale score of 25 or greater at baseline. The analysis includes data from placebocontrolled studies of reboxetine. Treatment groups were compared with respect to change from baseline for the mean HAM-D total score. An intent-to-treat analysis was used. Results: In placebo-controlled trials, reboxetine separated from placebo by week 1, and the difference from placebo was significant by week 4 in patients with severe depression. The differences between reboxetine and active comparators in these trials will be explored. Conclusions: These results indicate that reboxetine is significantly more effective than placebo among a subgroup of patients with severe depression at baseline. Reboxetine was at least as effective as fluoxetine and imipramine.
(pI.0241Premenstrual dysphoric disorder (PMDD) and work efficiency: Response to fluoxetine in a randomized clinical trial M. Steiner’, PT. Trzepacz’ *, E. Brown3. ‘St. Joseph’s Hospital McMasters University, Ontario, Canada; ‘Lilly Research Laboratories, Department of Neuroscience, Indianapolis, Indiana; 3Eli Lilly and Company Nederland, CO, USA Purpose: A DSM-IV diagnosis of PMDD, a severe form of premenstrual syndrome (PMS), requires interference with social and occupational functioning (school, home, job). Survey studies of PMS find that women have varying degrees of difficulty with work efficiency. However, there are no studies of perceived work efficiency for PMDD separate from the larger PMS population. We studied 320 women who met criteria for late-luteal phase dysphoric disorder (LLPDD) - the DSM-III-R version of PMDD - after 2 months of prospective daily symptom charting. Methods: We measured baseline follicular vs. luteal phase presence of patient-rated work efficiency-related symptoms on the Premenstrual Tension Scale-Self Rated (PMTS-SR) for: doubting own judgement, diminished efficiency, difficulty completing household/job routine, forgetful/unable to concentrate, more accidents with daily housework/job, clumsier, distractibility, and negative/hostile toward other people. Women were then randomized to double-blind treatment with either fluoxetine 20 mg/day, fluoxetine
PI Aflective disorders andantidepressants
Results: Statistically significant differences were not seen at end point; however, they were noted for response on the MADRS total and CGI-I scores, but not on the HAM-D. In addition, by week 4, venlafaxine was statistically significantly (P < 0.05) superior to fluoxetine and placebo in reducing the HAM-D depressed mood item. At week 4, a trend toward venlafaxine superiority in reducing the HAM-D psychic anxiety item was observed (P = 0.059). By week 6, MADRS response frequency was 55%, 36%, and 36% for venlafaxine, fluoxetine, and placebo, respectively (P < 0.05 venlafaxine vs placebo; P < 0.05 venlafaxine vs fluoxetine). By week 3, CGI-I response frequency was 50%, 41%, and 35% for venlafaxine, fluoxetine, and placebo, respectively (P < 0.05 venlafaxine vs placebo; P < 0.05 venlafaxine vs fluoxetine). A separate analysis of the MADRS data suggests that the superior efficacy of venlafaxine over fluoxetine or placebo increases in direct proportion to the baseline score (ie, the sicker the patient, the greater the venlafaxine efficacy). Venlafaxine produced a higher remission rate than fluoxetine and placebo (42%, 29%, and 38%, respectively), a trend level that did not reach statistical significance. Although the incidence of individual adverse events was modestly higher in the venlafaxine group, both venlafaxine and fluoxetine were well tolerated in these geriatric patients. Conclusion: Although significant differences in overall effects were not seen at week 8, venlafaxine showed increased response on CGI-I by week 3, depressed mood and psychic anxiety by week 4, and MADRS at week 6. These data suggest venlafaxine had a more rapid onset of action, demonstrating a significantly greater response than fluoxetine as early as week 3. No significant safety concerns were evident at the maximum administered doses of either study drug in these patients.
[P.1.022/ Effects of reboxetine on HAM-D factors among depressed patients J. Ferguson, J. Mendels, S. Montgomery, S. Stahl, G. Schwartz*. Pharmacia & Upjohn, Global Medical Aflairs, Peapack, New Jersey, USA Background: Reboxetine selectively blocks reuptake of noradrenaline and has been shown to be effective for the treatment of major depressive disorder. We have examined the effects of reboxetine on several HAM-D symptom clusters. Methods: The effects of reboxetine 8 to 10 mg/day on symptom clusters were examined from short-term, double-blind, randomized, placebo-controlled trials. Mean change from baseline at each assessment interval was determined for the anxiety factor (HAMD items 10, 11, 12, 13, 15, 17), insomnia factor (items 4, 5, 6), cognitive disturbance factor (items 2, 3 9, 19, 20, 21), and psychomotor retardation factor (items 1, 7, 8, 14). In addition, symptom clusters were examined for dichotomous changes associated with an increase or decrease in symptoms Tom baseline. Results: Significant improvements Tom baseline were observed for HAM-D anxiety factor I as early as day 14, and these improvements were maintained to the end of the trials. Significant improvements from baseline were also observed with reboxetine for other HAM-D symptom clusters, which will be reported in detail. Conclusion: Reboxetine was associated with substantial improvements from baseline in symptoms of anxiety, insomnia, cognition, and retardation. These results support the effectiveness of reboxetine for the treatment of major depression irrespective
of initial symptom profile and demonstrate additional beneficial improvements in specific symptom clusters.
)p.1.0231
Efficacy of reboxetine in patients with severe major depression
S. Montgomery, S. Stahl, J. Ferguson, J. Mendels, G. Schwartz*. Pharmacia & Upjohn, Global Medical Affairs, Peapack New Jersey, USA Background: Reboxetine is a novel antidepressant that selectively inhibits the reuptake of noradrenaline without significant effects on the serotonin transporter. Results from several placebocontrolled trials in patients with major depressive disorder have demonstrated efficacy for reboxetine. Although efficacy has been shown for the total group of depressed patients in clinical trials, we are presenting the analysis of a subset of patients with severe depression. Methods: An analysis was conducted of the efficacy of reboxetine in the subgroup of clinical trial participants with severe depression, defined as having a HAM-D Rating Scale score of 25 or greater at baseline. The analysis includes data from placebocontrolled studies of reboxetine. Treatment groups were compared with respect to change from baseline for the mean HAM-D total score. An intent-to-treat analysis was used. Results: In placebo-controlled trials, reboxetine separated from placebo by week 1, and the difference from placebo was significant by week 4 in patients with severe depression. The differences between reboxetine and active comparators in these trials will be explored. Conclusions: These results indicate that reboxetine is significantly more effective than placebo among a subgroup of patients with severe depression at baseline. Reboxetine was at least as effective as fluoxetine and imipramine.
(pI.0241Premenstrual dysphoric disorder (PMDD) and work efficiency: Response to fluoxetine in a randomized clinical trial M. Steiner’, PT. Trzepacz’ *, E. Brown3. ‘St. Joseph’s Hospital McMasters University, Ontario, Canada; ‘Lilly Research Laboratories, Department of Neuroscience, Indianapolis, Indiana; 3Eli Lilly and Company Nederland, CO, USA Purpose: A DSM-IV diagnosis of PMDD, a severe form of premenstrual syndrome (PMS), requires interference with social and occupational functioning (school, home, job). Survey studies of PMS find that women have varying degrees of difficulty with work efficiency. However, there are no studies of perceived work efficiency for PMDD separate from the larger PMS population. We studied 320 women who met criteria for late-luteal phase dysphoric disorder (LLPDD) - the DSM-III-R version of PMDD - after 2 months of prospective daily symptom charting. Methods: We measured baseline follicular vs. luteal phase presence of patient-rated work efficiency-related symptoms on the Premenstrual Tension Scale-Self Rated (PMTS-SR) for: doubting own judgement, diminished efficiency, difficulty completing household/job routine, forgetful/unable to concentrate, more accidents with daily housework/job, clumsier, distractibility, and negative/hostile toward other people. Women were then randomized to double-blind treatment with either fluoxetine 20 mg/day, fluoxetine